On his return to Europe between 1825 and 1828, Rugendas lived successively in Paris, Augsburg and Munich, with the aim of learning new art techniques, such as oil painting. There, he published from 1827 to 1835, with the help of Victor Aimé Huber, his monumental book Voyage Pittoresque dans le Brésil (Picturesque Voyage to Brazil), with more than 100 illustrations, which became one of the most important documents about Brazil in the 19th century. He also studied in Italy, visiting Pisa, Florence, Rome, Naples, Venice and Sicily. But inspired again by a noted explorer and naturalist, Alexander Humboldt (1769–1859), whom he once met, Rugendas sought financial support for a much more ambitious project of recording pictorially the life and nature of Latin America; in his words "an endeavour to truly become the illustrator of life in the New World". In 1831 he travelled first to Haiti, and then to Mexico. He began to use oil painting there, with excellent results. Unfortunately, Rugendas was incarcerated and expelled from the country after he became involved in a failed coup against Mexico's president, Anastasio Bustamante, in 1834.

From 1834 to 1844 he travelled to Chile, Argentina, Uruguay, Peru and Bolivia, and finally went back to Rio de Janeiro, in 1845. Well-accepted and feted by the court of Emperor Dom Pedro II, he executed portraits of several members of the royal court and participated in an artistic exposition.

At the age of 44, in 1846, Rugendas departed to Europe, never to return to Latin America. He died in Weilheim an der Teck, Germany, King Maximilian II of Bavaria having acquired most of his works in exchange for a life pension. His painting "Columbus taking Possession of the New World" (1855) is on view at the Neue Pinakothek, in Munich.